An increasing array of organic chemical reactions, e.g., acylations, alkylations, enolate additions, Wittig reactions, reductions, oxidations, etc., that are traditionally carried out in homogeneous solution are now being adapted for solid-phase synthesis. For this reason, there is a large demand for suitable polymeric supports. For the most well-studied case, i.e., solid-phase peptide synthesis (SPPS), a wide range of materials have been developed.
Mertifield's original studies, and much subsequent work, used low crosslinked polystyrene Merrifield, J. Am. Chem. Soc., 85 2149-2154 (1963)!. Polystyrene, however, is limited in the number and variety of solvents that can be used. Because peptide synthesis takes place within a well-solvated gel Sarin et al., J. Am. Chem. Soc. 102 5463-5470 (1980)!, one aspect that has been considered in the development of supports for SPPS is how well the material swells. To ensure good swelling properties, most polymeric supports used previously for this purpose have had a minimum amount of crosslinking consistent with mechanical stability. Generally, it is believed that the more crosslinking, the more mechanically stable is the polymer, but the less swellable it is. Thus, polymers used as solid supports have been developed to balance swelling with mechanical stability by using a low level of crosslinker (e.g., typically less than about 10 mole- % and usually only about 1-2 mole- %).
For SPPS, another consideration is to produce a support of the same polarity as the peptide backbone. Sheppard and coworkers developed a polyamide material known commercially as PEPSYN Arshady et al., J. Chem. Soc., Perkin Trans. I, 529-537 (1981)!. This material, however, has not been commercially successful. Another consideration, of particular importance for continuous-flow procedures, is the mechanical stability of the support. Efforts to develop materials for this purpose resulted in PEPSYN K Atherton et al., J. Chem. Soc., Chem. Commun., 336-337 (1981)! and polyamide-Polyhipe Small and Sherrington, J. Chem. Soc.. Chem. Commun., 1589-1591 (1989)!.
Earlier work in the area of solid-phase synthesis also focused on supports that comprise polyethylene glycol (PEG) grafted onto low crosslinked polystyrene (PS). The resultant PEG-PS can be used in continuous-flow processes, has good swelling properties, and shows good compatibility with peptides Zalipsky et al., React. Polym., 2, 243-258 (1994), and U.S. Pat. No. 5,235,028 (Barany et al.)!. Solid-phase peptide synthesis procedures and supports are summarized, for example, by G. Barany et al., Int. J. Peptide Protein Res. 30 705-739 (1987) and J. M. Stewart et al., Innovation and Perspectives in Solid Phase Synthesis: Peptides, Polypeptides, and Olizonucleotides. Macro-organic Reagents and Catalysts, R. Epton, Ed., SPCC UK Ltd., 1-9 (1990).
A need exists for other polymeric supports, particularly for solid- phase synthesis, but also for applications in chromatography, immobilization, etc.